1. Field of the Invention
The present invention generally relates to clinical in vitro proton (.sup.1 H) magnetic resonance spectroscopy (MRS). More specifically, the present invention is directed to the application of in vitro .sup.1 H magnetic resonance spectroscopy in a method to detect the past history of an individual's alcohol use (frequency and amount of consumption).
2. Related Art
Acquired alcohol tolerance in humans is proportional to the amount of ethanol consumed and the frequency of drinking (Mendelson & Mello, N. Engl. J. Med. 301:912-821 (1979); Kalant, H., in "Biology of Alcoholism", Kissin & Begleiter, eds., Plenum Press, New York, N.Y. (1971), pp. 1-26). The degree of chronic ethanol tolerance often is correlated with the severity of ethanol dependence, but alcohol tolerance may also develop in occasional drinkers who do not abuse alcohol and are not alcohol dependent.
The specific mechanisms which subserve the development of ethanol tolerance are unknown. A number of interrelated processes, including ethanol-induced changes in plasma membranes and membrane-bound water, probably are involved intolerance (Goldstein, D. B., Ann. N.Y. Acad. Sci. 492: 103-111 (1987); Hunt, W. A., "Alcohol and Biological Membranes," Guilford Press, New York N.Y. (1985), p. 3; Hoek & Taraschi, Trends Biochem. Sci. 13:269-274 (1988); Koob & Bloom, Science 242:715-723 (1988)). Binding of ethanol to hydrophilic phosphates of phospholipid head groups located on the surface of cell membranes may also vary as a function of ethanol tolerance as a consequence of the effects of ethanol on membrane phospholipid structures (Chin & Goldstein, Science 196:684-685 (1977); Rottenberg et al., Science 213:583-585 (1981); Taraschi et al., Proc. Natl. Acad. Sci. USA 83:3669-3673 (1986); Taraschi et al., Proc. Natl. Acad. Sci. USA 83:9398-9402 (1986); Waring et al., Proc. Natl. Acad. Sci. USA 78:2528-2586 1981); Tsai et al., Mol. Pharmacol. 31:623-630 (1987); Chiou et al., Science 248:583-585 (1990); Chiou et al., Alcohol 8:143-150 (1991)).
Proton MRS has been employed to qualitatively identify organic compounds, including ethanol, in human serum (Boch, J. L., "Analysis of serum by high-yield proton nuclear magnetic resonance," Clin. Chem. 28:1873-1877 (1982)). Boch suggests that proton MRS may also be used quantitatively to determine the concentration of some organic chemicals in human plasma by determining the areas under relevant peaks on the MRS chemical shift versus peak height spectrum.
Proton MRS has also been employed to study the effects of chronic alcohol on the water content of red blood cells. Besson, J. A. O. et al., ".sup.1 H-NMR Relaxation Times and Water Content of Red Blood Cells for Chronic Alcoholic Patients during Withdrawal," Magnetic Resonance Imaging 7:289-291 (1989) discloses that changes in T.sub.1 and T.sub.2 relaxation time occur in red blood cells in patients with chronic alcoholism. The reported results indicated that the T.sub.1 values for red blood cells of chronic alcoholics were significantly increased compared with controls. The T.sub.2 values for red blood cells of chronic alcoholics were also significantly increased compared with controls. The authors hypothesized that altered T.sub.1 reflects some disruption in the free-bound state of water, possibly secondary to membrane changes.
Besson, J. A. O. et al., "The Effects of Progressive Abstinence from Alcohol on Red Blood Cell Proton NMR Relaxation Times and Water Content," Alcoholism: Clinical and Experimental Research 15:181-183 (1991) discloses that red blood cell proton relaxation times T.sub.1 and T.sub.2 measured in abstinent chronic alcoholic patients, were elevated in the early stages of abstinence and declined to control values after eight weeks of abstinence. The authors also reported that T.sub.1 levels are increased in brain gray and white matter of chronic alcoholic individuals, with the T.sub.1 level falling toward control levels after 3 months.
Chiu, P. et al., "In vivo proton magnetic resonance spectroscopy detection of human alcohol tolerance," Magnetic Resonance in Medicine 32:511-515 (1994) discloses that brain-blood ethanol concentration ratios for heavy drinkers were significantly greater than brain-blood ethanol concentration ratios for occasional drinkers when brain ethanol concentration is measured by MRS. The reference suggests that in vivo brain MRS can be employed to discriminate between individuals who are alcohol tolerant (frequently consume alcohol) and alcohol non-tolerant (occasionally consume alcohol) individuals.
Kaufman, M. J. et al., "In vivo Proton Magnetic Resonance Spectroscopy of Alcohol and Rhesus Monkey Brain," Magnetic Resonance Imaging 12:1245-1253 (1994) describes measurement of brain alcohol levels in Rhesus monkeys by in vivo proton MRS following acute alcohol administration. The reference suggests that MRS-visibility of brain alcohol is related to the history of alcohol exposure and degree of alcohol tolerance of the non-human primate subject.
Harasymiv, U.S. Pat. No. 5,126,271 discloses a method for determining the consumption rate of alcohol by a human subject by developing a serum panel that includes at least twelve constituents. Two of the constituents are HDL and magnesium.
A need currently exists in the art for a routine screening method for objectively discriminating between individuals who are alcohol tolerant individuals (frequently consume alcohol) and alcohol non-tolerant (occasional drinkers) individuals. The in vivo brain MRS method suggested by Chiu et al. has the benefit of being non-invasive. However, many hospitals are not equipped with the necessary facilities to perform in vivo brain MRS imaging. The in vivo method also requires administration of ethanol to the subject. It would be preferable to avoid administering ethanol to a subject as part of a medical screening test.